Albumin, in particular human serum albumin (hereinafter referred to as "HSA"), is a principal proteinaceous constituent of the blood. The protein is produced in the liver and is responsible for the maintenance of normal osmotic pressure in the circulatory system. HSA also functions as a carrier for various serum molecules.
HSA is used under various clinical circumstances. For example, patients in shock or with serious burns generally require repeated administration of HSA to restore and maintain blood volume thereby alleviating several trauma-associated symptoms. Patients with hypoproteinemia or fetal erythroblastosis may sometimes require treatment with HSA.
Thus, in conditions in which fluid loss occurs, such as in the case of surgical operation, shock, burn or edema-inducing hypoproteinemia, HSA administration finds a beneficial utility.
At present HSA is produced in the main as a product of fractionation of the blood collected from donors. However, this production method is disadvantageous in that it is uneconomical and an ample supply of blood is often difficult to procure. Furthermore, there is the ever present risk of contamination with infectious agents as hepatitis virus. It will therefore be useful to develop a substitute means of obtaining HSA.
The advent of recombinant DNA technology has made it possible to produce a variety of useful polypeptides in microorganisms. Thus, a number of mammalian polypeptides are produced in prokaryotes, for example human growth hormone, interferons, vaccines, hormones, enzymes and antibodies.
To overcome some of the above-mentioned difficulties in the production of HSA, processes are being established for the large-quantity production of HSA by genetic engineering techniques and for the high-level purification of genetically engineered HSA. Some methods are known for the production of HSA by utilizing recombinant DNA technology with yeast as host organisms (EP-A-123544, EP-A-248637 and EP-A-251744).
However, in producing HSA and in purifying the same from genetically engineered microorganisms, the crude HSA-containing materials are necessarily contaminated by microbial components, in the main microbial proteins. These contaminants have not been removed to a satisfactory extent by those methods which are used for the preparation of plasma-derived HSA.